90 research outputs found

    Pound\u27s Progress: The Vortextual Evolution of Imagism and Its Poetic Image

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    Although previous Imagist scholarship considers its subject from chronological, technical, and historical viewpoints, rarely does it combine two-let alone all three-of those perspectives. Undoubtedly, each of those critical lenses contributes to the overall understanding of Imagism. Yet, by not weaving the technique and theory of Imagism into a linear account of its development, those studies tend to view those aspects of Imagism as if they were discrete and stable entities. To counteract that trend, this dissertation argues that Pound\u27s Imagist program-due to the ambiguity and developing definitions of several of its key terms-allowed the Imagist poets to produce a richly diverse form of Imagism that coexisted with, but was not necessarily contained by, Pound\u27s evolving concept of that program and its poetic Image. Specifically, by offering a chronological critical history of the technical and theoretical components of Pound\u27s concept of Imagism as they developed, this project highlights the transitive process wherein Pound\u27s Imagism both resulted from and created a poetic Vortex. Moreover, a close reading of the first Imagist anthology, Des Imagistes, illustrates how Pound\u27s super-positioned editorial arrangement of that collection allows it to function as an Imagist presentation of the varied origins, influences, and types of imagery existent within Pound\u27s version of the Imagist movement. Ultimately, then, this dissertation concludes that, due to the complex interaction between the individual interpretations of the Image made by the poets featured in Des Imagistes and the writers and literary traditions that influenced them, the anthological structure of that collection offers the most accurate presentation of the admixture of poetic fecundity and editorial pruning that defines Imagism

    Becoming Self: A Jungian Approach to Paradise Lost

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    When addressing Paradise Lost, the reader is not encountering static characters but is interacting with and being acted upon by highly symbolic manifestations of the primitive condition of humanity‟s collective psyche. In dealing with the figures of Christianity‟s mythos, John Milton creates a text that stimulates the collective unconscious of the reader and draws out the primordial expressions of the self—archetypal manifestations. Subsequently, these manifestations are projected back onto the figures within the text and the reader engages in a dynamic relationship with the poem as both the reader and the figures of Adam and Eve experience the process of individuation alongside one another. Carl Jung‟s archetypal theory offers a comprehensive blend of psychology and cultural anthropology with which to observe the individuation process, a four-stage psychological journey that involves an encounter with three archetypal manifestations: the shadow, the anima(us), and the wise old man or great mother. Each of the predominant characters of the text act as an external projection of these internal psychological forms as the reader, along with Adam and Eve, encounters first the shadow in the form of Satan, next the anima(us) in the form of the contra-sexual other—Eve for Adam and Adam for Eve, and finally the wise old man or great mother who is simultaneously a representation of the self in the figure of the triune God. In the end, Adam and Eve achieve a state of individuated self-hood through the union of God with man, which is realized in the figure of the Christ. This image is the final manifestation of the reader‟s individuated self, a psychological state of internal and external harmony

    Mind the Gap: A Tribute to David Logan on His Retirement

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    Impact of Fill-Finish Process on Protein Formulation in the Absence of Stabilizing Agents

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    Optimization of the fill-finish process for a biotherapeutic is imperative for the highest quality drug product. Chemical and physical degradation must be fully characterized as an enzyme progresses towards commercialization to design a fully optimized process. To avoid degradation and/or sensitivity to the filling process of an enzyme, pharmaceutical scientists utilize stabilizing excipients as tools to mitigate known chemical or structural weaknesses; however, little work has been published on process-related stabilization techniques when the route of administration dictates the exclusion of key stabilizing excipients. The goal of this thesis is to provide guidance in selecting key factors impacting enzyme stability in fill-finish processes in the absence of excipients. The effect of shear stress applied to an enzyme solution was studied in the presence of various interfacial phenomenon between solution and surface of air, stainless steel and tubings commonly used in manufacturing. Although interfacial interactions and aggregation pathways are considered to be enzyme-specific, this work will allow researchers to focus on key conditions affecting stability of proteins in this process. Factors studied here include exposure of the formulation to shear stress from several models with increasing interfacial complexity. The most simplistic model applied a specific shear stress through a microfluidic chip, exposing the enzyme solution to high levels of shear for a short period of time. A cone and plate rotational rheometer was used to study shear applied to an enzyme solution for up to ten minutes with the addition of an air-water interface. Lastly, a recirculation model was employed to study the interaction with tubing surfaces and the shear stresses caused by peristaltic pumping over time. Several analytical assays were employed to understand destabilization caused by these stress models, and were extended to lead to an overall understanding of the impact of various process-related stresses. An enzyme solution exhibits the most dramatic change when exposed to the peristaltic recirculation pumping model, with the most significantly destabilizing factor being the use of a thermoplastic elastomer tubing surface. The other shear stress models did not produce trends in measured responses, indicating that the associated levels of stress with these models are below the amount necessary to irreversibly alter stability. Methods to measure and characterize aggregation for the recirculation models across a large dynamic range showed dramatic changes with increasing exposure time, resulting in increased aggregate populations over the length of pumping time. The flow imaging data captured high levels of particles shed from the tubing material in the 1-100 µm size-range. These particles could act as heterogeneous nucleation sites, and could explain the increase in aggregation in enzyme solution with these tubing types. The presence of unique multimeric soluble enzyme aggregates was observed in the thermoplastic elastomer tubings, indicating not only that they are deleterious in terms of colloidal stability, but presumably they are formed via different pathways. Silicone tubings performed to a higher standard in recirculation models than thermoplastic tubings. Silicone tubings produced a very low amount of subvisible particulate shedding, undetectable multimeric aggregate species, and a better overall visual appearance after recirculation for up to four hours. In summary, notable enzyme solution instability was not related to the stress of shear in a flow field alone, but rather the use of an incompatible tubing material in the fill-finish process

    1, 2-Bis (phenylsulfonyl)-1H-Indole as an Acceptor of Organocuprate Nucleophiles

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    1,2-Bis(phenylsulfonyl)-1H-indole is a novel example of an electron-deficient indole that undergoes nucleophilic attack at C-3. Though a variety of other organometallic nucleophiles fail to engender nucleophilic substitution, organocuprates produce 3-substituted 2-(phenylsulfonyl)-1H-indoles. These reactions contribute to the growing number of examples of nucleophilic addition to the indole core

    All-Atomic Molecular Dynamic Studies of Human and Drosophila CDK8: Insights into Their Kinase Domains, the LXXLL Motifs, and Drug Binding Site

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    Cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC) play conserved roles in modulating RNA polymerase II (Pol II)-dependent gene expression. To understand the structure and function relations of CDK8, we analyzed the structures of human and Drosophila CDK8 proteins using molecular dynamics simulations, combined with functional analyses in Drosophila. Specifically, we evaluated the structural differences between hCDK8 and dCDK8 to predict the effects of the LXXLL motif mutation (AQKAA), the P154L mutations, and drug binding on local structures of the CDK8 proteins. First, we have observed that both the LXXLL motif and the kinase activity of CDK8 are required for the normal larval-to-pupal transition in Drosophila. Second, our molecular dynamic analyses have revealed that hCDK8 has higher hydrogen bond occupation of His149-Asp151 and Asp151-Asn156 than dCDK8. Third, the substructure of Asp282, Phe283, Arg285, Thr287 and Cys291 can distinguish human and Drosophila CDK8 structures. In addition, there are two hydrogen bonds in the LXXLL motif: a lower occupation between L312 and L315, and a relatively higher occupation between L312 and L316. Human CDK8 has higher hydrogen bond occupation between L312 and L316 than dCDK8. Moreover, L312, L315 and L316 in the LXXLL motif of CDK8 have the specific pattern of hydrogen bonds and geometries, which could be crucial for the binding to nuclear receptors. Furthermore, the P154L mutation dramatically decreases the hydrogen bond between L312 and L315 in hCDK8, but not in dCDK8. The mutations of P154L and AQKAA modestly alter the local structures around residues 154. Finally, we identified the inhibitor-induced conformational changes of hCDK8, and our results suggest a structural difference in the drug-binding site between hCDK8 and dCDK8. Taken together, these results provide the structural insights into the roles of the LXXLL motif and the kinase activity of CDK8 in vivo

    Management of recurrent coxofemoral luxation in a miniature horse

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    In July 2013, a miniature horse presented to the Cornell University Equine and Farm Animal Hospital Orthopedic Surgery Service with the complaint of acute, non-weight bearing lameness of the right hind limb. A coxofemoral luxation was diagnosed using a combination of physical exam, radiographic and computer tomography findings. The luxation was surgically reduced and secured with an extra-capsular suture technique using screws and fiber wire. Within 48 hours, the repair had failed and re-luxation occurred. The horse was again brought for surgical repair of the luxation using a similar technique using additional wire and screws. 72 hours later the horse luxated a third time, and a femoral head and neck ostectomy was elected. Following the third surgery an infection developed with multiple drug resistant bacteria cultured from the site. Stent bandages that had previously been covering the incision site were replaced with a sterile vacuum-assisted wound closure system to aid in removal of purulent drainage from the site, and antibiotics were chosen based on susceptibility results from the culture. Breakdown of the left hind limb suspensory mechanisms began to occur with the prolonged reduced weight bearing of the right hind limb. This was addressed through various techniques, including pain management, shoeing, and physical therapy to encourage use of the right hind limb. Over the next few weeks management for pain, infection, and breakdown of the opposite leg was performed with positive initial results. However, about one month after the initial presentation to the Cornell Equine and Farm Animal Hospital, the horse suffered an episode of a sudden increase in pain and discomfort, reverting to almost complete non-weight bearing lameness. Radiographs and CT evaluation were performed to rule out causes of the sudden increase in pain, with the only notable finding being contact between the femur and acetabulum. A femoral and sciatic nerve block were performed using EMG to attempt to isolate pain and rule out neuropathic causes, and an epidural catheter was placed for regular infusion of pain medication. Eventually the horse became refractory to all increases in pain management and therapy that was attempted, and the owner elected euthanasia and necropsy

    ChemInform Abstract: Metalation of Pyrrole

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